rs113716376

Variant names:

• chr15-77614077-G-A
• rs113716376
• NM_032808.7:c.1830C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_032808.7(LINGO1):​c.1830C>T​(p.Asp610Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00161 in 1,610,260 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0080 (18 hom., cov: 33)
  • Exomes 𝑓: 0.00094 (20 hom.)
• Consequence: LINGO1 NM_032808.7 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.06
• Publications: 2 publications found

Genes affected

LINGO1 (HGNC:21205): (leucine rich repeat and Ig domain containing 1) Predicted to enable epidermal growth factor receptor binding activity. Predicted to act upstream of or within generation of neurons and protein kinase B signaling. Predicted to be located in plasma membrane. Predicted to be active in extracellular matrix and extracellular space. Implicated in autosomal recessive non-syndromic intellectual disability and glaucoma. [provided by Alliance of Genome Resources, Apr 2022]

LINGO1 Gene-Disease associations (from GenCC):

• intellectual disability, autosomal recessive 64

  Inheritance: AR, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

LOC105370906 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 15-77614077-G-A is Benign according to our data. Variant chr15-77614077-G-A is described in ClinVar as Benign. ClinVar VariationId is 779902.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.07 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00798 (1215/152304) while in subpopulation AFR AF = 0.0268 (1114/41564). AF 95% confidence interval is 0.0255. There are 18 homozygotes in GnomAd4. There are 586 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 18 Unknown,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032808.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINGO1	NM_032808.7	MANE Select	c.1830C>T	p.Asp610Asp	synonymous	Exon 2 of 2	NP_116197.4
	LINGO1	NM_001301186.2		c.1812C>T	p.Asp604Asp	synonymous	Exon 6 of 6	NP_001288115.1	Q96FE5-2
	LINGO1	NM_001301187.2		c.1812C>T	p.Asp604Asp	synonymous	Exon 6 of 6	NP_001288116.1	Q96FE5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINGO1	ENST00000355300.7	TSL:1 MANE Select	c.1830C>T	p.Asp610Asp	synonymous	Exon 2 of 2	ENSP00000347451.6	Q96FE5-1
	LINGO1	ENST00000561030.5	TSL:1	c.1812C>T	p.Asp604Asp	synonymous	Exon 4 of 4	ENSP00000453853.1	Q96FE5-2

Frequencies

GnomAD3 genomes AF: 0.00798 AC: 1214 AN: 152186 Hom.: 18 Cov.: 33

Gnomad AFR AF: 0.0269

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00451

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.00574

GnomAD2 exomes AF: 0.00218 AC: 522 AN: 239226 AF XY: 0.00180

Gnomad AFR exome AF: 0.0295

Gnomad AMR exome AF: 0.00161

Gnomad ASJ exome AF: 0.000203

Gnomad EAS exome AF: 0.0000579

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000234

Gnomad OTH exome AF: 0.000852

GnomAD4 exome AF: 0.000942 AC: 1373 AN: 1457956 Hom.: 20 Cov.: 31 AF XY: 0.000862 AC XY: 625 AN XY: 724986

African (AFR) AF: 0.0277 AC: 925 AN: 33386

American (AMR) AF: 0.00176 AC: 77 AN: 43812

Ashkenazi Jewish (ASJ) AF: 0.000307 AC: 8 AN: 26044

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39530

South Asian (SAS) AF: 0.0000699 AC: 6 AN: 85890

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53188

Middle Eastern (MID) AF: 0.00226 AC: 13 AN: 5762

European-Non Finnish (NFE) AF: 0.000186 AC: 206 AN: 1110074

Other (OTH) AF: 0.00227 AC: 137 AN: 60270

GnomAD4 genome AF: 0.00798 AC: 1215 AN: 152304 Hom.: 18 Cov.: 33 AF XY: 0.00787 AC XY: 586 AN XY: 74462

African (AFR) AF: 0.0268 AC: 1114 AN: 41564

American (AMR) AF: 0.00451 AC: 69 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000294 AC: 20 AN: 68020

Other (OTH) AF: 0.00568 AC: 12 AN: 2114

Alfa AF: 0.00508 Hom.: 5

Bravo AF: 0.00948

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	5.1
DANN	Benign	0.81
PhyloP100		-1.1
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs113716376; hg19: chr15-77906419;